期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 101, 期 9, 页码 1265-1269出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2007.06.004
关键词
aluminum; human neural cells; inflammation; iron; micro RNA; reactive oxygen species; RNA polymerase II; ROS; sulfates
资金
- NIA NIH HHS [R01 AG038834, AG 18031, R01 AG018031, R01 AG018031-05S1] Funding Source: Medline
Iron- and aluminum-sulfatc together, at nanomolar concentrations, trigger the production of reactive oxygen species (ROS) in cultures of human brain cells. Previous studies have shown that following ROS induction, a family of pathogenic brain genes that promote inflammatory signalling, cellular apoptosis and brain cell death is significantly over-expressed. Notably, iron- and aluminum-sulfate induce genes in cultured human brain cells that exhibit expression patterns similar to those observed to be up-regulated in moderate-to late-stage Alzheimer's disease (AD). In this study we have extended our investigations to analyze the expression of micro RNA (miRNA) populations in iron- and aluminum-sulfate treated human neural cells in primary culture. The main finding was that these ROS-generating neurotoxic metal sulfates also up-regulate a specific set of miRNAs that includes miR-9, miR-125b and miR-128. Notably, these same miRNAs are up-regulated in AD brain. These findings further support the idea that iron- and aluminum-sulfates induce genotoxicity via a ROS-mediated up-regulation of specific regulatory elements and pathogenic genes that redirect brain cell fate towards progressive dysfunction and apoptotic cell death. (c) 2007 Elsevier Inc. All rights reserved.
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